Mutagenetix > Incidental Mutation

Incidental Mutation 'R8528:Map3k4'

658910

Institutional Source

Beutler Lab

Gene Symbol

Map3k4

Ensembl Gene

ENSMUSG00000014426

Gene Name

mitogen-activated protein kinase kinase kinase 4

Synonyms

T-associated sex reversal, D17Rp17, D17Rp17e, Mekk4, Tas, RP17, MAPKKK4, MTK1

MMRRC Submission

068498-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.958) question?

Stock #

R8528 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

12446508-12537683 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 12451821 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Asparagine to Serine at position 1489 (N1489S)

Ref Sequence

ENSEMBL: ENSMUSP00000086459 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000089058]

AlphaFold

O08648

Predicted Effect

probably damaging
Transcript: ENSMUST00000089058
AA Change: N1489S

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000086459
Gene: ENSMUSG00000014426
AA Change: N1489S

Domain	Start	End	E-Value	Type
low complexity region	8	21	N/A	INTRINSIC
low complexity region	27	43	N/A	INTRINSIC
low complexity region	215	235	N/A	INTRINSIC
low complexity region	432	462	N/A	INTRINSIC
low complexity region	1177	1191	N/A	INTRINSIC
S_TKc	1332	1590	1.41e-91	SMART

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.9%

Validation Efficiency

100% (40/40)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]
PHENOTYPE: Homozygous null mice exhibit some perinatal lethality and survivors appear smaller. On certain genetic backgrounds, heterozygous X/Y mice may develop as phenotypic females or hermaphrodites. The sex-reversal phenotype is dependent on a combination of strain-specific autosomal and Y-linked alleles. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 42 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrb1	A	C	15: 74,447,700 (GRCm39)	I169L	possibly damaging	Het
Ahnak	A	T	19: 8,985,092 (GRCm39)	K2125N	probably damaging	Het
Arl5b	T	A	2: 15,078,138 (GRCm39)		probably null	Het
Ccng2	T	C	5: 93,417,164 (GRCm39)	V60A	possibly damaging	Het
Cfap65	A	G	1: 74,945,096 (GRCm39)	V1442A	possibly damaging	Het
Cyp1b1	T	A	17: 80,017,993 (GRCm39)	E387D	probably damaging	Het
Dchs2	T	C	3: 83,261,918 (GRCm39)	S2729P	probably damaging	Het
Dnah11	A	G	12: 117,972,538 (GRCm39)	F2882S	probably damaging	Het
Dpy30	T	C	17: 74,606,757 (GRCm39)	D97G	probably benign	Het
Enam	T	A	5: 88,650,078 (GRCm39)	V454E	probably damaging	Het
Eppk1	C	T	15: 75,994,319 (GRCm39)	R854Q	probably benign	Het
Ero1b	T	A	13: 12,614,757 (GRCm39)	C240*	probably null	Het
Exog	A	G	9: 119,291,686 (GRCm39)	D297G	probably damaging	Het
Fbxl12	C	A	9: 20,550,160 (GRCm39)	R165L	possibly damaging	Het
Fer1l5	A	G	1: 36,456,855 (GRCm39)	Y1611C	possibly damaging	Het
Firrm	T	C	1: 163,813,652 (GRCm39)	K191E	probably damaging	Het
Frmpd1	T	C	4: 45,285,034 (GRCm39)	V1285A	probably benign	Het
Gfpt1	G	C	6: 87,043,770 (GRCm39)		probably null	Het
Gm15446	T	C	5: 110,090,896 (GRCm39)	Y383H	possibly damaging	Het
Gsdmc	A	T	15: 63,649,189 (GRCm39)		probably null	Het
Hao1	A	G	2: 134,364,913 (GRCm39)	I238T	probably damaging	Het
Kcnq5	G	A	1: 21,549,648 (GRCm39)	R360C	probably damaging	Het
Kcnv2	T	A	19: 27,300,387 (GRCm39)	D79E	probably benign	Het
Lrrc8a	T	C	2: 30,145,557 (GRCm39)	Y124H	probably damaging	Het
Lrrc8d	T	A	5: 105,960,352 (GRCm39)	M254K	probably benign	Het
Mapk8ip2	A	G	15: 89,339,422 (GRCm39)	D34G	probably damaging	Het
Myo9a	A	G	9: 59,767,423 (GRCm39)	T876A	probably damaging	Het
Pabpc2	C	T	18: 39,908,439 (GRCm39)	T568I	probably benign	Het
Pcdhga2	G	T	18: 37,802,221 (GRCm39)	A22S	probably benign	Het
Rc3h2	G	A	2: 37,272,811 (GRCm39)	T755I	probably benign	Het
Sertad4	A	G	1: 192,533,391 (GRCm39)	V15A	probably benign	Het
Slc28a2	A	G	2: 122,286,223 (GRCm39)	K520E	probably damaging	Het
Slc4a10	T	C	2: 62,127,140 (GRCm39)	V831A	possibly damaging	Het
Sorbs1	G	C	19: 40,365,244 (GRCm39)	R180G	probably benign	Het
Spag17	A	T	3: 100,031,501 (GRCm39)	I2255F	possibly damaging	Het
Sprn	C	T	7: 139,733,423 (GRCm39)		probably benign	Het
Stim1	T	C	7: 102,080,289 (GRCm39)		probably benign	Het
Stk24	C	A	14: 121,529,447 (GRCm39)	A402S	probably benign	Het
Sycp2	A	G	2: 178,016,326 (GRCm39)	L712P	probably damaging	Het
Tenm3	C	T	8: 48,795,668 (GRCm39)	G269S	probably damaging	Het
Zdbf2	A	G	1: 63,342,545 (GRCm39)	E308G	possibly damaging	Het
Zfp442	A	C	2: 150,250,962 (GRCm39)	H312Q	probably damaging	Het

Other mutations in Map3k4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01065:Map3k4	APN	17	12,451,877 (GRCm39)	missense	probably damaging	1.00
IGL01124:Map3k4	APN	17	12,474,087 (GRCm39)	missense	probably benign	0.01
IGL01125:Map3k4	APN	17	12,490,849 (GRCm39)	missense	probably damaging	0.96
IGL01585:Map3k4	APN	17	12,467,846 (GRCm39)	missense	probably damaging	1.00
IGL02194:Map3k4	APN	17	12,482,815 (GRCm39)	missense	probably damaging	1.00
IGL02194:Map3k4	APN	17	12,467,882 (GRCm39)	missense	probably benign	0.30
IGL02292:Map3k4	APN	17	12,454,045 (GRCm39)	missense	possibly damaging	0.77
IGL02326:Map3k4	APN	17	12,467,897 (GRCm39)	missense	probably damaging	1.00
IGL02388:Map3k4	APN	17	12,490,497 (GRCm39)	missense	probably damaging	0.99
IGL02621:Map3k4	APN	17	12,482,900 (GRCm39)	missense	probably damaging	1.00
IGL02668:Map3k4	APN	17	12,454,840 (GRCm39)	missense	possibly damaging	0.85
IGL02850:Map3k4	APN	17	12,490,801 (GRCm39)	missense	probably damaging	1.00
IGL02939:Map3k4	APN	17	12,491,036 (GRCm39)	missense	probably damaging	1.00
IGL03148:Map3k4	APN	17	12,457,045 (GRCm39)	missense	probably benign	0.01
IGL03238:Map3k4	APN	17	12,490,045 (GRCm39)	missense	probably benign	0.10
ANU74:Map3k4	UTSW	17	12,451,863 (GRCm39)	missense	probably damaging	1.00
R0012:Map3k4	UTSW	17	12,457,076 (GRCm39)	missense	probably damaging	1.00
R0012:Map3k4	UTSW	17	12,457,076 (GRCm39)	missense	probably damaging	1.00
R0128:Map3k4	UTSW	17	12,466,950 (GRCm39)	missense	probably damaging	0.99
R0183:Map3k4	UTSW	17	12,454,015 (GRCm39)	missense	probably damaging	1.00
R0309:Map3k4	UTSW	17	12,489,902 (GRCm39)	frame shift	probably null
R0355:Map3k4	UTSW	17	12,473,058 (GRCm39)	missense	probably damaging	1.00
R0367:Map3k4	UTSW	17	12,476,928 (GRCm39)	splice site	probably benign
R1103:Map3k4	UTSW	17	12,455,950 (GRCm39)	splice site	probably null
R1446:Map3k4	UTSW	17	12,475,681 (GRCm39)	nonsense	probably null
R1542:Map3k4	UTSW	17	12,454,793 (GRCm39)	missense	probably damaging	0.97
R1713:Map3k4	UTSW	17	12,468,458 (GRCm39)	missense	probably benign	0.39
R1777:Map3k4	UTSW	17	12,490,617 (GRCm39)	missense	possibly damaging	0.82
R1797:Map3k4	UTSW	17	12,482,906 (GRCm39)	missense	probably benign	0.30
R1997:Map3k4	UTSW	17	12,473,882 (GRCm39)	critical splice donor site	probably null
R2042:Map3k4	UTSW	17	12,496,870 (GRCm39)	missense	probably damaging	0.99
R2878:Map3k4	UTSW	17	12,482,954 (GRCm39)	missense	probably benign	0.00
R2939:Map3k4	UTSW	17	12,480,157 (GRCm39)	missense	probably damaging	0.98
R2940:Map3k4	UTSW	17	12,480,157 (GRCm39)	missense	probably damaging	0.98
R3405:Map3k4	UTSW	17	12,475,668 (GRCm39)	missense	probably damaging	1.00
R3930:Map3k4	UTSW	17	12,454,880 (GRCm39)	missense	possibly damaging	0.83
R4291:Map3k4	UTSW	17	12,474,147 (GRCm39)	missense	probably benign	0.08
R4410:Map3k4	UTSW	17	12,467,885 (GRCm39)	missense	probably damaging	1.00
R4632:Map3k4	UTSW	17	12,451,391 (GRCm39)	missense	probably damaging	1.00
R4641:Map3k4	UTSW	17	12,482,932 (GRCm39)	missense	probably damaging	1.00
R4726:Map3k4	UTSW	17	12,451,851 (GRCm39)	missense	possibly damaging	0.89
R4730:Map3k4	UTSW	17	12,467,861 (GRCm39)	missense	probably damaging	0.99
R4832:Map3k4	UTSW	17	12,490,667 (GRCm39)	missense	probably damaging	1.00
R4896:Map3k4	UTSW	17	12,490,906 (GRCm39)	missense	possibly damaging	0.65
R4934:Map3k4	UTSW	17	12,490,787 (GRCm39)	missense	probably damaging	1.00
R4971:Map3k4	UTSW	17	12,468,382 (GRCm39)	critical splice donor site	probably null
R4980:Map3k4	UTSW	17	12,490,958 (GRCm39)	missense	probably damaging	1.00
R5211:Map3k4	UTSW	17	12,451,321 (GRCm39)	missense	possibly damaging	0.88
R5337:Map3k4	UTSW	17	12,490,497 (GRCm39)	missense	probably damaging	0.99
R5356:Map3k4	UTSW	17	12,466,195 (GRCm39)	missense	possibly damaging	0.87
R5550:Map3k4	UTSW	17	12,462,445 (GRCm39)	nonsense	probably null
R5824:Map3k4	UTSW	17	12,448,526 (GRCm39)	missense	probably damaging	1.00
R5890:Map3k4	UTSW	17	12,490,303 (GRCm39)	missense	probably damaging	1.00
R6285:Map3k4	UTSW	17	12,482,945 (GRCm39)	missense	probably damaging	1.00
R6380:Map3k4	UTSW	17	12,490,954 (GRCm39)	missense	possibly damaging	0.56
R6383:Map3k4	UTSW	17	12,468,470 (GRCm39)	missense	possibly damaging	0.82
R6571:Map3k4	UTSW	17	12,461,579 (GRCm39)	missense	possibly damaging	0.80
R6584:Map3k4	UTSW	17	12,479,378 (GRCm39)	missense	probably damaging	1.00
R6616:Map3k4	UTSW	17	12,490,231 (GRCm39)	missense	probably damaging	1.00
R6644:Map3k4	UTSW	17	12,451,297 (GRCm39)	critical splice donor site	probably null
R6909:Map3k4	UTSW	17	12,489,872 (GRCm39)	missense	probably damaging	1.00
R6947:Map3k4	UTSW	17	12,479,456 (GRCm39)	nonsense	probably null
R6970:Map3k4	UTSW	17	12,467,803 (GRCm39)	missense	probably damaging	1.00
R7120:Map3k4	UTSW	17	12,490,354 (GRCm39)	missense	probably damaging	1.00
R7253:Map3k4	UTSW	17	12,490,955 (GRCm39)	missense	probably benign	0.00
R7267:Map3k4	UTSW	17	12,490,536 (GRCm39)	nonsense	probably null
R7322:Map3k4	UTSW	17	12,489,833 (GRCm39)	missense	probably damaging	1.00
R7522:Map3k4	UTSW	17	12,480,219 (GRCm39)	missense	probably benign	0.39
R7554:Map3k4	UTSW	17	12,451,300 (GRCm39)	missense	probably damaging	1.00
R7554:Map3k4	UTSW	17	12,451,301 (GRCm39)	nonsense	probably null
R7681:Map3k4	UTSW	17	12,537,430 (GRCm39)	missense	unknown
R7734:Map3k4	UTSW	17	12,482,998 (GRCm39)	missense	probably damaging	1.00
R7842:Map3k4	UTSW	17	12,490,030 (GRCm39)	missense	possibly damaging	0.54
R8013:Map3k4	UTSW	17	12,489,918 (GRCm39)	nonsense	probably null
R8014:Map3k4	UTSW	17	12,489,918 (GRCm39)	nonsense	probably null
R8235:Map3k4	UTSW	17	12,458,968 (GRCm39)	splice site	probably null
R8294:Map3k4	UTSW	17	12,537,500 (GRCm39)	missense	unknown
R8858:Map3k4	UTSW	17	12,490,759 (GRCm39)	missense	probably damaging	1.00
R8924:Map3k4	UTSW	17	12,490,433 (GRCm39)	missense	probably benign	0.00
R9063:Map3k4	UTSW	17	12,482,878 (GRCm39)	missense	probably damaging	1.00
R9224:Map3k4	UTSW	17	12,456,973 (GRCm39)	missense	probably damaging	0.99
R9446:Map3k4	UTSW	17	12,451,375 (GRCm39)	missense	probably damaging	1.00
R9486:Map3k4	UTSW	17	12,489,860 (GRCm39)	missense	probably damaging	1.00
R9488:Map3k4	UTSW	17	12,489,860 (GRCm39)	missense	probably damaging	1.00
R9591:Map3k4	UTSW	17	12,454,795 (GRCm39)	missense	possibly damaging	0.91
R9617:Map3k4	UTSW	17	12,476,871 (GRCm39)	missense	possibly damaging	0.67
R9722:Map3k4	UTSW	17	12,490,523 (GRCm39)	missense	probably benign	0.01
X0067:Map3k4	UTSW	17	12,482,981 (GRCm39)	missense	probably benign	0.03
Z1177:Map3k4	UTSW	17	12,490,584 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CCAGGTACAGGCAGCAAATG -3'
(R):5'- TGTGAACATCTTGAGATACCCAC -3'

Sequencing Primer
(F):5'- CGACTTGAGGGACATTTTAGGGAC -3'
(R):5'- GAGATACCCACATTGTGTCTCAGAG -3'

Posted On

2021-01-18